Local trials helped in FDA approval of lupus drug

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Amy Clawson was unable to do much of anything with her hands. "My fingertips had ulcerations," she said. "They were very sore."

On top of that, Mrs. Clawson, 38, of Derry, was tired "all the time. I didn't have any energy." Her appetite was poor and she lost weight. Sometimes she had joint pain in her legs.

When she was 32, the cause of her problems was diagnosed: She had lupus, a chronic and potentially fatal disease with no known cure.

With lupus, something goes wrong with the immune system, which normally provides protection against foreign bodies such as bacteria and viruses; it instead attacks healthy tissue. The results can be inflammation, pain and damage in any part of the body. Symptoms worsen during periods called "flares."

The Lupus Foundation of America estimates that at least 1.5 million Americans have the disease, of which there are four types. Mrs. Clawson has the most common type: systemic lupus erythematosus.

Women are more often affected than men, and African-American women have been reported to be three times more likely to have lupus than white women.

Standard treatments include immunosuppressants, antimalarial medicines and corticosteroids. Mrs. Clawson said she tried them all.

Finally, Mrs. Clawson's rheumatologist, Fotios Koumpouras, then at the University of Pittsburgh but now medical director of the Lupus Center of Excellence in the West Penn Allegheny Health System, asked her if she'd like to participate in a medical study.

She said OK.

He entered her in a trial in which he was participating for patients with her variety of lupus. Conducted and paid for by Human Genome Services with development partner GlaxoSmithKline, it was looking at a new drug called belimumab, used in conjunction with the standard therapy. Dr. Koumpouras' Pitt colleague Susan Manzi, now director of the WPAHS lupus center, helped to design the trials.

The two drug companies provided financial support for the costs of the part of the trial conducted at Pitt, and Dr. Manzi was a paid consultant as a member of a medical advisory board.

On March 9, the Food and Drug Administration approved use of belimumab, now called Benlysta, for patients with SLE who are receiving standard therapy. The FDA said the drug was the first specifically approved to treat lupus since 1955.

The earlier drugs were Plaquenil (hydroxychloroquine) and corticosteroids. Aspirin was approved to treat lupus in 1948.

"Benlysta may be helpful for some lupus patients," an FDA spokeswoman wrote in an email. She noted that in U.S. trials, a larger percentage of participants receiving a monthly dose of Benlysta showed improvement compared to participants receiving a placebo. Patients in both groups received their standard medications as well.

"I think it is an historic event for lupus, for lupus patients, for lupus doctors. It's the first time we've had a drug specifically designed, studied and approved for lupus," said rheumatologist Anca D. Askanase, assistant professor, New York University School of Medicine, NYU Hospital for Joint Diseases, and a member of the lupus foundation's Medical-Scientific Advisory Council.

Dr. Askanase explained that the drugs the FDA approved for lupus so many decades ago were borrowed from other diseases.

And other drugs used for other diseases also have been tried on lupus, Dr. Manzi said, including chemotherapies and transplant rejection drugs.

"We've had many failures. That's why this is such a huge story," she said.

But after about a decade of trials involving more than 2,000 participants, it will not come cheap.

Barry Labinger, executive vice president and chief commercial officer of Human Genome Sciences, said that the cost over an "average year" will be about $35,000. That's for monthly intravenous infusions plus one additional infusion at the beginning of treatment. The doses are based on the weight of patient, and Mr. Labinger figured the average cost on a weight of 160 pounds.

He said he expected most insurances to cover the cost. For those insurance companies who pass on part of the price, he said, "we have a couple different programs to defray those costs.

"So our goal is to make sure affordability doesn't get in the way of patients having access to it."

Mrs. Clawson didn't know if her insurance would cover it but she responded, "oh, yes" when she was asked if she intended to keep taking it.

The study she was in was double blind, meaning neither patients nor researchers knew who was taking Benlysta and who was taking a placebo. But Mrs. Clawson said that after a "good year" of infusions she began to feel better.

The trial ended in 2009, Dr. Koumpouras said, but Mrs. Clawson was given and took the option of going into an open-label study that gave her continued access to the drug.

"I have no ulceration at all on my hands. I can work with my hands a little better now," she said. "My flareups are not there too much, like when I got really tired, had no energy, like when my legs started hurting, joint pain. I haven't had any of that for a while.

"Now I'm pretty much free to do about anything, except, of course, be in the sun for a long time." Sunlight can trigger skin rashes in people with lupus.

But Benlysta is not a cure, Dr. Manzi stressed.

"It reduces disease activity," she said. "It was not developed as a cure. It was developed to keep the disease under control."

It does that by inhibiting the activity of B cells, the cells that make the autoantibodies that attack the patient's own tissue.

Specifically, Benlysta targets a circulating protein called BLyS that binds to the B cells and keeps them alive. The drug blocks BLyS, also called the B-lymphocyte stimulator, from binding to the B cells, which then die. When the B cells are inactive, the production of autoantibodies falls, and the disease improves, Dr. Manzi said.

Benlysta's activity puts the drug into the category of biologic therapies, she said. Human Genome Sciences discovered the BLyS protein in 1996.

"I think it definitely is going to benefit many, but ... there are people who shouldn't take it, and there are people we don't know if it works," Dr. Askanase said. "I can't say I'm going to give it to everybody, but I'm going to try it in a lot of them."

The FDA, which looked at two Phase 3 studies involving 1,684 lupus sufferers, reported in its news release about Benlysta's approval that African-American patients did not appear to respond to treatment with the drug, but the two studies lacked enough numbers to form conclusions.

The drug sponsor agreed to do a separate study on the effect of Benlysta on African-Americans. "We don't believe there is any difference, but we'll do the study to determine that for sure," Mr. Labinger said.

"We all have African-American patients it works for," Dr. Koumpouras said.

The drug makers acknowledged and the FDA noted that there were more deaths and serious infections within the patients who were treated with Benlysta compared to the placebo group. "The drug should not be administered with live vaccines," the FDA warned.

The most commonly reported side effects included nausea, diarrhea, fever, inflammation of the nose and/or pharynx, bronchitis, insomnia, pain in extremities, depression, and migraines.

Mrs. Clawson said she has had no side effects.

There is hope that the makers' success with Benlysta will prompt additional research and development of drugs to combat the confounding disease. Dr. Askanase said she knew of two stage 3 trials and others in earlier stages currently in progress. "I think it makes sense to hope for that because if one drug is successful it's proof of concept; it can work," she said.

"It's such a complex disease that affects so many organs, no one drug is going to help every patient. We're going to need a panel of agents to turn to," Dr. Manzi said.